Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


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Actualités et Publications

Stage M2 en Synthèse


Dans la continuité de nos travaux menés sur la synthèse de glycoconjugués régulateurs de l’inflammation, nous recrutons un stagiaire de Master 2 à partir de février 2022 pour 6 mois. Nous visons particulièrement le récepteur TLR4 connu pour être un interrupteur biologique déclenchant une partie de la réponse immunitaire. Présent dans le cerveau également, il agit sur la neuro-inflammation et est donc une cible pour les patients atteints de pathologies pour lesquelles une suractivité inflammatoire est constatée (Maladie d’Alzheimer, de Parkinson ou encore la Sclérose en plaque).

Metal-free hydroxy and aminocyanation of furanos-3-uloses,

Camara, T. E.; Koffi Teki, D. S.-E.; Chagnault, V.

Carbohydr. Res. 2021, 108486.

TSAO-T and ATSAO-T analogues are molecules of interest that are able to inhibit the reverse transcriptase (RT) of HIV-1 and HCV. We also recently highlighted their antiproliferative properties. In all cases, the spiro cycle was a required group for biological activities, which led chemists to produce many derivatives, especially on this ring. These structures can be accessed through the formation of glycoaminonitriles and glycocyanhydrins using methodologies not always adapted to the synthesis of large quantities. Moreover, these latter are poorly versatile (substrate-dependent), need expensive cyanogenic agents and implies the use of a metal in non-catalytic amounts. For this reason, we report here a new metal-free methodology for the synthesis of glycoaminonitriles and glycocyanhydrins using molecular iodine (I2).

Cyclodextrin Complexation as a Way of Increasing the Aqueous Solublity and Staility of Carvedilol,

Rigaud, S.; Mathiron, D.; Moufawad, T.; Landy, D.; Djedaini-Pilard, F.; Marçon, F.

Pharmaceutics 2021, 13, 1746.

We studied the effect of several CDs on carvedilol’s solubility and chemical stability in various aqueous media. Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of γCD or RAMEB in an aqueous medium with an acceptable acid pH (between 3.5 and 4.7). Carvedilol formed 1:1 inclusion complexes but those with RAMEB appear to be stronger (K = 317 M−1 at 298 K) than that with γCD (K = 225 M−1 at 298 K). The complexation of carvedilol by RAMEB significantly increased the drug’s photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol.

Chemical Evaluation, Antioxidant, Antiproliferative, Anti-Inflammatory and Antibacterial Activities of Organic Extract and Semi-Purified Fractions of the Adriatic Sea Fan, Eunicella cavolini,

Matulja, D.; Grbcic, P.; Bojanic, K.; Topic-Popovic, N.; Coz-Rakovac, R.; Laclef, S.; Smuc, T.; Jovic, O.; Markovic, D.; Pavelic, S. K.

Molecules 2021, 26.

Due to sedentary lifestyle and harsh environmental conditions, gorgonian coral extracts are recognized as a rich source of novel compounds with various biological activities, of interest to the pharmaceutical and cosmetic industries. The presented study aimed to perform chemical screening of organic extracts and semi-purified fractions obtained from the common Adriatic gorgonian, sea fan, Eunicella cavolini (Koch, 1887) and explore its abilities to exert different biological effects in vitro. Qualitative chemical evaluation revealed the presence of several classes of secondary metabolites extended with mass spectrometry analysis and tentative dereplication by using Global Natural Product Social Molecular Networking online platform (GNPS). Furthermore, fractions F4 and F3 showed the highest phenolic (3.28 +/- 0.04 mg GAE/g sample) and carotene (23.11 +/- 2.48 mg beta-CA/g sample) content, respectively. The fraction F3 inhibited 50% of DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and ABTS (2,2'-azino-bis (3-ethylbenzthiazolin-6-yl) sulfonic acid) radicals at the concentrations of 767.09 +/- 11.57 and 157.16 +/- 10.83 microg/mL, respectively. The highest anti-inflammatory potential was exhibited by F2 (IC50 = 198.70 +/- 28.77 microg/mL) regarding the inhibition of albumin denaturation and F1 (IC50 = 254.49 +/- 49.17 microg/mL) in terms of soybean lipoxygenase inhibition. In addition, the most pronounced antiproliferative effects were observed for all samples (IC50 ranging from 0.82 +/- 0.14-231.18 +/- 46.13 microg/mL) against several carcinoma cell lines, but also towards non-transformed human fibroblasts pointing to a generally cytotoxic effect. In addition, the antibacterial activity was tested by broth microdilution assay against three human pathogenic bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The latter was the most affected by fractions F2 and F3. Finally, further purification, isolation and characterization of pure compounds from the most active fractions are under investigation.

Low-Valent Calix[4]arene Glycoconjugates Based on Hydroxamic Acid Bearing Linkers as Potent Inhibitors in a Model of Ebola Virus Cis-Infection and HCMV-gB-Recombinant Glycoprotein Interaction with MDDC Cells by Blocking DC-SIGN,

Chakroun, K.; Taouai, M.; Porkolab, V.; Luczkowiak, J.; Sommer, R.; Cheneau, C.; Mathiron, D.; Ben Maaouia, M. A.; Pilard, S.; Abidi, R.; Mullie, C.; Fieschi, F.; Cragg, P. J.; Halary, F.; Delgado, R.; Benazza, M.

J. Med. Chem. 2021.

In addition to a variety of viral-glycoprotein receptors (e.g., heparan sulfate, Niemann-Pick C1, etc.), dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), from the C-type lectin receptor family, plays one of the most important pathogenic functions for a wide range of viruses (e.g., Ebola, human cytomegalovirus (HCMV), HIV-1, severe acute respiratory syndrome coronavirus 2, etc.) that invade host cells before replication; thus, its inhibition represents a relevant extracellular antiviral therapy. We report two novel p-tBu-calixarene glycoclusters 1 and 2, bearing tetrahydroxamic acid groups, which exhibit micromolar inhibition of soluble DC-SIGN binding and provide nanomolar IC50 inhibition of both DC-SIGN-dependent Jurkat cis-cell infection by viral particle pseudotyped with Ebola virus glycoprotein and the HCMV-gB-recombinant glycoprotein interaction with monocyte-derived dendritic cells expressing DC-SIGN. A unique cooperative involvement of sugar, linker, and calixarene core is likely behind the strong avidity of DC-SIGN for these low-valent systems. We claim herein new promising candidates for the rational development of a large spectrum of antiviral therapeutics.

Ring-Opening of Cyclodextrins: An Efficient Route to Pure Maltohexa-, Hepta-, and Octaoses,

Pélingre, M.; Koffi Teki, D. S.-E.; El-Abid, J.; Chagnault, V.; Kovensky, J.; Bonnet, V.

Organics 2021, 2, 287-305.

Many preparations of maltooligosaccharides have been described in literature, essentially using enzymatic or biotechnological processes. These compounds, derived from starch, are well-known as prebiotic agents. The use of maltohexa-, hepta-, and octaoses as synthons in organic synthesis was also well documented in literature. They can indeed be obtained as single compounds by the cyclodextrins’ ring-opening. This reaction has been studied for many years, varying the protecting and functional groups and the reaction conditions, leading to functionalized oligomaltoses. These compounds are of wide interest in various fields. They have a strong potential as scaffolds for multivalence in chemobiology, as building blocks for the production of biomimetic pseudo-glycopeptides, as well as monomers for the preparation of materials. In view of the importance of these oligomaltoses, this review focuses on the different methodologies allowing access to them via chemical and enzymatic ring-opening of cyclodextrins.

Pilot-scale direct UV-C photodegradation of pesticides in groundwater and recycled wastewater for agricultural use,

Ferhi, S.; Vieillard, J.; Garau, C.; Poultier, O.; Demey, L.; Beaulieu, R.; Penalva, P.; Gobert, V.; Portet-Koltalo, F.

Journal of Environmental Chemical Engineering 2021, 9, 106120.

Pesticides widely used for intensive agriculture may leach to groundwater and pose problems to drinking water and irrigation. UV-C disinfection systems (UV-DS) for water disinfection can be used also for the abatement of organic micropollutants. A pilot-scale continuous flow-through UV-DS system was evaluated for its degradation efficiency of atrazine (ATR), malathion (MAL) and glyphosate (GLY) from 40 L water. Groundwater used to irrigate potato fields and recycled wastewater used to wash potatoes were treated without catalysts to avoid any toxicity effect on potatoes. Chromatographic methods were used to quantify very low pesticide levels before and after UV-C treatments (<10 µg L−1), while a specific method was adapted to analyse traces of GLY (0.0008–10 µg L−1) in recycled wastewater containing suspended particulate matter (SPM). ATR was completely eliminated from groundwater after 15 min photodegradation while 80% was removed from the turbid wastewater after 25 min. For MAL, 70–80% was removed in 25 min from the groundwater. For wastewater, the initial concentration was important for the performance of the photolytic process. An amount of 75% of GLY was eliminated after 10 min irradiation at concentrations higher than those found in natural groundwater. In wastewater, the UV-C treatment was less efficient because GLY was mainly adsorbed to SPM which obstruct the photodegradation process. Therefore, the pilot-scale UV-DS using a turbulent flow and a multiple-lamp system was performed to remove quantitatively traces of pesticides from large volumes of water, by direct photolytic oxidation, when the turbidity of the treated water was limited.

Design, Synthesis and Antibacterial Activity Evaluation of 4,5-Diphenyl-1H-Imidazoles Derivatives,

Bamoro, C.; Bamba, F.; Steve-Evanes, K. T. D.; Aurélie, V.; Vincent, C.

Open Journal of Medicinal Chemistry 2021, 11, 17-26.

Due to the continuous emergence and rapid spread of drug-resistant strains of bacteria, there is an urgent need for the development of novel antimicrobials. Along this line, the synthesis and antibacterial activity of 4,5-diphenylimidazol-2-thiol derivatives 2a-g and 6a-e are reported. The structures of the synthesized compounds were confirmed by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS). All compounds were screened in vitro for their antibacterial activity against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria) and also against Staphyloccocus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed most of the synthesized compounds have no antibacterial activity. However compound 6d was two-fold potent than ciprofloxacin against Staphylococcus aureus with Minimum Inhibitory Concentration (MIC) of 4 μg/mL and 6c showed moderate biological activity against Staphylococcus aureus (16 μg/mL) and Enterococcus faecalis (16 μg/mL).

Protein–Protein Interface Topology as a Predictor of Secondary Structure and Molecular Function Using Convolutional Deep Learning,

Bouvier, B.

J. Chem. Inf. Model. 2021.

To power the specific recognition and binding of protein partners into functional complexes, a wealth of information about the structure and function of the partners is necessarily encoded into the global shape of protein–protein interfaces and their local topological features. To identify whether this is the case, this study uses convolutional deep learning methods (typically leveraged for 2D image recognition) on 3D voxel representations of protein–protein interfaces colored by burial depth. A novel two-stage network fed with voxelizations of each interface at two distinct resolutions achieves balance between performance and computational cost. From the shape of the interfaces, the network tries to predict the presence of secondary structure motifs at the interface and the molecular function of the corresponding complex. Secondary structure and certain classes of function are found to be very well predicted, validating the hypothesis that interface shape is a conveyor of higher-level information. Interface patterns triggering the recognition of specific classes are also identified and described.

IL versus DES: Impact on chitin pretreatment to afford high quality and highly functionalizable chitosan,

Huet, G.; Hadad, C.; González-Domínguez, J. M.; Courty, M.; Jamali, A.; Cailleu, D.; van Nhien, A. N.

Carbohydr. Polym. 2021, 269, 118332.

Chitin is mainly extracted from crustaceans, but this resource is seasonally dependent and can represent a major drawback to satisfy the traceability criterion for high valuable applications. Insect resources are valuable alternatives due to their lower mineral content. However, the deacetylation of chitin into chitosan is still an expensive process. Therefore, we herein compare the impact of both DES/IL-pretreatments on the efficiency of the chemical deacetylation of chitin carried out over two insect sources (Bombyx eri, BE and Hermetia illucens, HI) and shrimp shells (S). The results showed that chitosans obtained from IL-pretreated chitins from BE larva, present lower acetylation degrees (13–17%) than DES-pretreated samples (18–27%). A selective N-acylation reaction with oleic acid has also been performed on the purest and most deacetylated chitosans leading to high substitution degrees (up to 27%). The overall approach validates the proper chitin source and processing methodology to achieve high quality and highly functionalizable chitosan.

Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources
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